Cytopathology of amyotrophic lateral sclerosis: A personal perspective of recent developments

Abstract

Amyotrophic lateral sclerosis (ALS) is an age-associated neurodegenerative disease that primarily involves the motor neuron system. Despite this disease having been studied for over 100 years, its etiology is still unknown and no specific diagnostic laboratory test is available. The diagnosis of ALS is therefore based on clinical and/or neuropathological findings with loss and degeneration of the large anterior horn cells of the spinal cord being the principal and most salient features. Several symposia and workshops on the cytopathology of ALS were held within the last 2 year period, which reflects the many new and important developments taking place. Although loss of motor neurons has been well-known for many years, cytoplasmic alterations of the lower motor neurons have been studied in detail only in recent years by applying immunohistochemical and electron microscopic procedures. The purpose of this review is to introduce some of the novel findings associated with lower motor neuron alterations.

Immunohistochemical Study on Superoxide Dismutases in Spinal Cords from Autopsied Patients with Amyotrophic Lateral Sclerosis

“…Several studies on ALS have been described for over 100 years [1]. Recent applications of molecular biologi cal techniques to the ALS research suggested that some change of SOD 1 protein may bear relation to a process of this disease [1, 3 -5 , 16-19], However, the patho genic role of SOD1 abnormalities in ALS is still in con troversy.…”

“…Amyotrophic lateral sclerosis (ALS) is an age-depen dent fatal neurodegenerative disorder that mainly involves upper and lower motor neurons [ 1 ]. ALS is subclassified into the sporadic form, the familial form and detoxifies superoxide radical to form hydrogen peroxide and molecular oxygen [II, 12J.…”

Disruption of the structure of the Golgi apparatus and the function of the secretory pathway by mutants G93A and G85R of Cu, Zn superoxide dismutase (SOD1) of familial amyotrophic lateral sclerosis

“…Amyotrophic Lateral Sclerosis is a chronic and invariably fatal disease, characterized by a progressive loss of motor functions and degeneration of motor neurons in the spinal cord, brain stem, and motor cortex [1]. The discovery of mutations in the gene encoding the Cu/Zn superoxide dismutase 1 (SOD1) in certain cases of familial ALS, and the generation of a transgenic mouse model for the disease, provided the hope for understanding the pathogenesis, and developing therapies [2][3][4].…”

Dysregulation of Stathmin, a Microtubule-Destabilizing Protein, and Up-Regulation of Hsp25, Hsp27, and the Antioxidant Peroxiredoxin 6 in a Mouse Model of Familial Amyotrophic Lateral Sclerosis

“…(Am J Pathol 2004, 165:1701-1718) Amyotrophic lateral sclerosis (ALS) is a world-wide, fatal neurodegenerative disease characterized by loss of motor neurons in the cerebral cortex, brain stem, medulla, and spinal cord and by the proliferation of astrocytes. 1 The annual incidence of sporadic ALS in nonendemic areas is 1.0 per 100,000. 2,3 Among the indigenous population of Guam, ALS occurs frequently in combination with parkinsonism and dementia.…”